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United States Patent | 6,004,799 |
Luciw ,   et al. | December 21, 1999 |
This invention discloses live-attenuated feline immunodeficiency virus (FIV), and recombinant vectors for producing them, useful as vaccines and therapeutic agents against FIV and diseases associated with virulent FIV infection. In the recombinant vectors and FIVs, one or more genes, or part of the gene(s), responsible for FIV pathogenesis have been completely or partially rendered nonfunctional, e.g., by full or partial deletion or mutagenesis. These anti-FIV vaccines may be given to susceptible hosts in the form of infectious virus or cloned DNA.
Inventors: | Luciw; Paul A. (Davis, CA); Sparger; Ellen E. (Dixon, CA) |
Assignee: | The Regents of the University of California (Oakland, CA) |
Appl. No.: | 811828 |
Filed: | March 5, 1997 |
Current U.S. Class: | 424/205.1; 424/93.2; 424/192.1; 424/208.1; 435/5; 435/235.1; 435/320.1; 536/23.1 |
Intern'l Class: | C12N 007/04; A61K 039/00; C12Q 001/70; C07H 021/02 |
Field of Search: | 424/192.1,208.1 435/5,172.3,236 536/23.1 |
Foreign Patent Documents | |||
WO 92/00987 | Jan., 1992 | WO | . |
WO 94/17825 | Aug., 1994 | WO | . |
WO 95/04546 | Feb., 1995 | WO | . |
WO 95/16784 | Jun., 1995 | WO | . |
Benvenisty, N. et al., "Direct introduction of genes into rats and expression of the genes," Proc. Natl. Acad. Sci. U.S.A. 83:9551-9555 (1986). Clements, J.E. et al., "Molecular biology of lentiviruses," Sem. Virol. 3:137-146 (1992). Diehl, L.J. et al., "Longitudinal Assessment of Feline Immunodeficiency Virus Kinetics in Plasma by Use of a Quantitative Competitive Reverse Transcriptase PCR," J. Virol. 69(4):2328-2332 (1995). Giavedoni, L.D. et al., "SIV.sub..DELTA.nef expressing INF-.gamma. is a more attenuated and efficacious vaccine than SIV.sub..DELTA.nef," 13th Ann. Symp. Nonhuman Primate Models for AIDS, Nov. 5-8, 1994, Monterey, CA, Abstract 24. Ho, S.N. et al., "Site-directed mutagenesis by overlap extension using the polymerase chain reaction," Gene 7:51-59 (1989). Hosie, M.J., "The Development of a Vaccine Against Feline Immunodeficiency Virus," Br. vet. J. 150:25-39 (1994). Lawrence, C.E. et al., "Decreased mitogen responsiveness and elevated tumor necrosis factor production in cats shortly after feline immunodeficiency virus infection," Vet. Immunol. Immunopath. 35:51-59 (1992). Letvin, N.L. et al., "Risks of handling HIV," Nature 349:573 (1991). Luria, S. et al., "Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated inductionof interleukin 2 mRNA," Proc. Natl. Acad. Sci. U.S.A. 88:5326-5330 (1991). Mayo, K.E. et al., "The Mouse Metallothionein-I Gene is Transcriptionally Regulated by Cadmium following Transfection into Human or Mouse Cells," Cell 29:99-108 (1982). Miyazawa, T. et al., "The AP-1 binding site in the feline immunodeficiency virus long terminal repeat is not required for virus replication in feline T Lymphocytes," J. Gen. Virol. 74:1573-1580 (1993). Montelaro, R.C. et al., "Vaccines against Retroviruses," The Retroviridae vol. 4, J.A. Levy, ed., Plenum Press, New York, pp. 605-656 (1995). Nicolau, C. et al., "In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I," Proc. Natl. Acad. Sci. U.S.A. 80:1068-1072 (1983). Olmsted, R.A. et al., "Molecular cloning of feline immunodeficiency virus," Proc. Natl. Acad. Sci. U.S.A. 86:2448-2452 (1989). Phillips, T.R. et al., "Comparison of Two Host Cell Range Variants of Feline Immunodeficiency Virus," J. Virol. 64(10):4605-4613 (1990). Portis, J.L. et al., "Infectivity of Retroviral DNA In Vivo," J. Acq. Immune Deficiency Syndromes 5:1272-1277 (1992). Shacklett, B.L. et al., "Analysis of the VIF Gene of Feline Immunodificiency Virus," Virology 204:860-867 (1994). Seeger, C. et al., "The cloned genome of ground squirrel hepatitis virus is infectious in the animal," Proc. Natl. Acad. Sci. U.S.A. 81:5849-5852 (1984). Sparger, E.E. et al., "Regulation of Gene Expression Directed by the Long Terminal Repeat of the Feline Immunodeficiency Virus," Virology 187:165-177 (1992). Sparger, E.E. et al., "Infection of Cats with Molecularly Cloned and Biological Isolates of the Feline Immunodeficiency Virus," Virology 205:546-553 (1994). Talbott, R.L. et al., "Nucleotide sequence and genomic organization of feline immunodeficiency virus," Proc. Natl. Acad. Sci. U.S.A. 86:5743-5747 (1989). Thompson, F.J. et al., "Cis- and trans-regulation of feline immunodeficiency virus: identificationof functional binding sites in the long terminal repeat," J. Gen. Virol. 75:545-554 (1994). Tomonaga, K. et al., "The Feline Immunodeficiency Virus ORF-A Gene Facilitates Efficient Virla Replication in Established T-Cell Lines and Peripheral Blood Lymphocytes," J. Virol. 67(10):5889-5895 (1993). Ulmer, J.B. et al., "Heterologous Protection Against Influenza by Injection of DNA Encoding a Viral Protein," Science 259:1745-1749 (1993). Wolff, J.A. et al., "Direct Gene Transfer into Mouse Muscle in Vivo," Science 247:1465-1468 (1990). Wu, G.Y. et al., "Receptor-mediated Gene Delivery and Expression in Vivo," J. Biol. Chem. 263(29):14621-14624 (1988). Yamamoto, J.K. et al., "Experimental Vaccine Protection Against Feline Immunodeficiency Virus," AIDS Res. and Human Retroviruses 7(11):911-922 (1991). T. Yilma et al. Abstract from "Conference On Advances In AIDS Vaccine Development", 8th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS, Feb. 11-15, 1996. |
TABLE 1 ______________________________________ Detection of Virus in SPF Cats Inoculated With FIV-pPPR LTR Mutant Viruses Virus Virus Isolation Weeks Post Inoculum Animal Inoculum 2 4 8 12 18 33 ______________________________________ 256 pSVWT -.sup.a 10.sup.6 10.sup.6 10.sup.6 10.sup.5 - 267 pSVWT 10.sup.6 10.sup.5 10.sup.4 10.sup.4 10.sup.4 10.sup.5 274 pSVWT - - - - - - 293 pSVWT 10.sup.6 10.sup.5 10.sup.6 10.sup.5 10.sup.5 10.sup.6 298 pSVWT 10.sup.6 10.sup.6 10.sup.5 10.sup.4 10.sup.5 10.sup.3 257 pSV.DELTA.AP1 10.sup.6 10.sup.6 10.sup.5 10.sup.5 10.sup.6 10.sup.5 268 pSV.DELTA.AP1 10.sup.6 - 10.sup.3 10.sup.4 10.sup.5 10.sup.6 275 pSV.DELTA.AP1 10.sup.6 10.sup.6 10.sup.4 10.sup.3 10.sup.4 - 294 pSV.DELTA.AP1 10.sup.6 10.sup.5 10.sup.5 10.sup.5 10.sup.4 10.sup.6 299 pSV.DELTA.AP1 - 10.sup.5 10.sup.5 10.sup.5 10.sup.4 - 265 pSV.DELTA.ATF - - - - 10.sup.4 10.sup.5 269 pSV.DELTA.ATF 10.sup.6 - 10.sup.5b 10.sup.5 10.sup.5 10.sup.5 276 pSV-ATF 10.sup.6b - 10.sup.6b 10.sup.5b 10.sup.6b 10.sup.5 295 pSV.DELTA.ATF 10.sup.6b 10.sup.5 - - - - 301 pSV-ATF 10.sup.6b 10.sup.5 - 10.sup.5b 10.sup.4 10.sup.4 266 pSV.DELTA.AP1/ATF 10.sup.6b - - - - - 273 pSV.DELTA.AP1/ATF 10.sup.6 10.sup.5 - - - - 292 pSV.DELTA.AP1/ATF - - - - 10.sup.6b - 296 pSV.DELTA.AP1/ATF - - - - - - 302 pSV.DELTA.AP1/ATF - - - - - - 144 Control - - - - - - 145 Control - - - - - - 146 Control - - - - - - 147 Control - - - - - - ______________________________________ .sup.a Virus isolations were performed by cultivation of serial dilutions of harvested PBMC from each cat at each time point and carried out for 28 days with the exception of time point 18 weeks PI which was carried out for 56 days. The symbol (-) indicates virus was not isolated from any of PBMC dilutions cultured whereas a number value represents the lowest concentration of cells from which virus could be isolated by day 28 (56 for 18 weeks PI) in culture. .sup.b Virus was not detected until day 28 or later in culture.
TABLE 2 __________________________________________________________________________ Dectection of FIV p24 Antibody In SPF Cats Inoculated with FIV-pPPR LTR Mutant Viruses Virus Serum Antibody.sup.a Weeks Post Inoculum Animal Inoculum 0 2 4 6 8 10 12 14 16 33 __________________________________________________________________________ 256 pSVWT - - - - + + + + + + 267 pSVWT - - - + + + + + + + 274 pSVWT - - - - - - - - - - 293 pSVWT - - - + + + + + + + 298 pSVWT - - - - - + + + + + 257 pSV.DELTA.AP1 - - - + + +/- + + + + 268 pSV.DELTA.AP1 - - - + + + + + + + 275 pSV.DELTA.AP1 - - - +/-.sup.b - +/- + + + + 294 pSV.DELTA.AP1 - - - + + + + + + + 299 pSV.DELTA.AP1 - - - + + + + + + + 265 pSV.DELTA.ATF - - - - - - - +/- + + 269 pSV.DELTA.ATF - - - + + + + + + + 276 pSV.DELTA.ATF - - - +/- +/- + + + + + 295 pSV.DELTA.ATF - - - - - - - - - - 301 pSV.DELTA.ATF - - - + + + + + + + 266 pSV.DELTA.AP1/ATF - - - + + + + + + + 273 pSV.DELTA.AP1/ATF - - - + + + + + + + 292 pSV.DELTA.AP1/ATF - - - - +/- +/- +/- +/- + + 296 pSV.DELTA.AP1/ATF - - - - - - - - - - 302 pSV.DELTA.AP1/ATF - - - - - - - - + + 144 Control - - - - - - - - - - 145 Control - - - - - - - - - - 146 Control - - - - - - - - - - 147 Control - - - - - - - - - - __________________________________________________________________________ .sup.a Serum antibody to recombinant FIV p24 was assayed by an FIV p24 antibody ELISA. .sup.b +/- designates an indeterminate result.
TABLE 3 ______________________________________ Detection of Virus In SPF Cats Infected with FIV-pPPR LTR Mutant Viruses and Challenged with Biological FIV-PPR Virus Isolation Weeks Post Challenge Virus (Post Infection) Animal Inoculum 0 (42).sup.a 3 (50) 5 (52) 8 (55) ______________________________________ 266 pSV.DELTA.AP1/ATF -.sup.b 10.sup.5 (ND).sup.c 10.sup.5 (Mut).sup.c 10.sup.5 (Mut).sup.c 273 pSV.DELTA.AP1/ATF - - 10.sup.4 (ND).sup.c 10.sup.4 (Mut).sup.c 292 pSV.DELTA.AP1/ATF - - - - 296 pSV.DELTA.AP1/ATF - - 10.sup.6 (WT) 10.sup.6 (WT) 302 pSV.DELTA.AP1/ATF - - 10.sup.5 (ND).sup.c 10.sup.3 (Mut).sup.c 144 Control - - 10.sup.6 10.sup.4 145 Control - 10.sup.4 10.sup.3 10.sup.3 146 Control - 10.sup.4 10.sup.4 10.sup.3 147 Control - 10.sup.3 10.sup.3 10.sup.4 ______________________________________ .sup.a Number above reflects weeks post challenge with biological FIVPPR whereas lower number in parentheses designates time post infection with W or mutant virus. .sup.b Virus isolations were performed on serial dilutions of harvested PBMC from each cat at each time point as described for Table 1 except isolations carried out for 42 days. The symbol (-) indicates virus was no isolated from any of PBMC dilutions cultured whereas a number value represents the lowest concentration of cells from which virus could be isolated by day 42 in culture. .sup.c Virus was not detected until day 28 or later in culture. Virus genotype is noted in parentheses and was determined by nucleotide sequencing of amplified LTR sequences from cultivated PBMC. Mut indicates isolated virus was mutant and was identified as pSV.DELTA.AP1/ATF by LTR DNA sequence and WT indicates that the isolated virus was wild type (challenge). ND indicates that sequence is not determined at this time.
TABLE 4 ______________________________________ Detection of FIV p24 Antibody In SPF Cats Inoculated With Molecularly Cloned FIV-pPPR Proviral DNA Inoculum Serum Antibody.sup.a Weeks Post Inoculum Animal and Route 0 2 4 6 8 10 12 14 15 ______________________________________ 479 300 .mu.g IM.sup.b - - - + + + + + + 521 300 .mu.g IM - - - - + + + + + 522 300 .mu.g IM - - - - +/-.sup.c + + + + 337 100 .mu.g IM - - - +/- + + + + + 438 100 .mu.g IM - - - +/- + + + + + 523 100 .mu.g IM - - - - - +/- + + + 333 30 .mu.g IM - - - - - - + + + 477 30 .mu.g IM - - - - +/- - - - - 499 30 .mu.g IM - - - - +/- + + + + 336 30 .mu.g ID.sup.d - - - - - + + + + 473 30 .mu.g ID - - - - - - - - - 536 30 .mu.g ID - - - - - - - - ______________________________________ .sup.a Serum antibody to recombinant FIV p24 was assayed by an FIV p24 antibody ELISA. .sup.b IM designates intramuscular injection. .sup.c +/- designates an indeterminate result. .sup.d ID designates intradermal injection.
TABLE 5 ______________________________________ Detection of Virus In SPF Cats Inoculated With Molecularly Cloned FIV-pPPR Proviral DNA Inoculum Virus Isolation.sup.a Weeks Post Inoculum Animal and Route 2 4 8 12 15 ______________________________________ 479 300 .mu.g IM - + - + (10.sup.5).sup.b + (10.sup.3) 521 300 .mu.g IM - + - + (10.sup.6) + (10.sup.5) 522 300 .mu.g IM - + - + (10.sup.5) + (10.sup.5) 337 100 .mu.g IM - + + + (10.sup.5) + (10.sup.6) 438 100 .mu.g IM - + + + (10.sup.5) + (10.sup.4) 523 100 .mu.g IM - - + + (10.sup.5) + (10.sup.5) 333 30 .mu.g IM - - + + (10.sup.6) + (10.sup.5) 477 30 .mu.g IM - - - - - 499 30 .mu.g IM - - + - + (10.sup.6) 336 30 .mu.g ID - - + - + (10.sup.6) 473 30 .mu.g ID - - - - - 536 30 .mu.g ID - - - - - ______________________________________ .sup.a PBMC were harvested from each cat, stimulated with concanavalin A for 3 days, and cultivated in the presence of IL2. Supernatant was collected twice weekly from PBMC cultures for 4 weeks post cultivation an assessed for FIVp24 by an FIV p24 capture ELISA. .sup.b Virus isolations were performed on serial dilutions of harvested PBMC from each cat at this time point. The value in the parentheses represents the lowest concentration of cells from which virus could be isolated.
TABLE 6 __________________________________________________________________________ Post Challenge Virus Load Pre-Challenge Antibody Post Challenge (# Infected cells Cat No. Inoculum Virus Recovery Response Virus Recovery per 1 million cells) __________________________________________________________________________ 468 pSV AP1/ATF No Yes AP1/ATF <1 479 pSV AP1/ATF Yes Yes None <1 481 pSV AP1/ATF Yes Yes AP1/ATF 10 487 pSV AP1/ATF No No AP1/ATF <1 488 pSV AP1/ATF Yes Yes AP1/ATF 1 491 pSV AP1/ATF No No Wild Type 10 469 pSV WT Yes Yes Wild Type 10 478 pSV WT Yes Yes Wild Type 10 480 pSV WT Yes Yes Wild Type 10 482 pSV WT Yes Yes Wild Type >1000 489 pSV WT Yes Yes Wild Type 100 470 Control Yes Yes Wild Type Not Done 471 Control Yes Yes Wild Type <1 472 Control Yes Yes Wild Type Not Done 484 Control Yes No Negative Not Done 486 Control Yes Yes Wild Type <1 __________________________________________________________________________
__________________________________________________________________________ # SEQUENCE LISTING - - - - (1) GENERAL INFORMATION: - - (iii) NUMBER OF SEQUENCES: 14 - - - - (2) INFORMATION FOR SEQ ID NO:1: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline - #Immunodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: - - GCGTTGGGAG CTCTCCCATA TGAATCC - # - # 27 - - - - (2) INFORMATION FOR SEQ ID NO:2: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 57 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: - - CTGCTAGCGC TTTAACTATG TGTTCAGCTG TTTCCATTTA TCATTTGTTT - # 50 - - GTGACAG - # - # - # 57 - - - - (2) INFORMATION FOR SEQ ID NO:3: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 53 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: - - GATAAATGGA AACAGCTGAA CACATAGTTA AAGCGCTAGC AGCTGCTTAA - # 50 - - CCG - # - # - # 53 - - - - (2) INFORMATION FOR SEQ ID NO:4: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 40 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus and pGEM5Zf(+- #) - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: - - GTCGGTCGAC TGCGAAGTTC TCGGCCCGGA TTCCGAGACC - # - # 40 - - - - (2) INFORMATION FOR SEQ ID NO:5: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 54 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: circular - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: - - CTTACAGTGG AGCAAATTAT CATTGGCAAG CTTTACATAG GATGTGGTTT - # 50 - - TGCG - # - # - # 54 - - - - (2) INFORMATION FOR SEQ ID NO:6: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 43 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: - - CCTATGTAAA GCTTGCCAAG TATAATTTGC TCCACTGTAA GAG - # - # 43 - - - - (2) INFORMATION FOR SEQ ID NO:7: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: - - CTGTCGGGCG CCAACTGCGA AGTTCTCGGC CCGGATTCCG AG - # - # 42 - - - - (2) INFORMATION FOR SEQ ID NO:8: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: - - GGACTAGTTG GGATGAGTAT TGGGACCCTG - # - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:9: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 45 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: SV40 geno - #me-early enhancer and promoter - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: - - GACGAGAGCT CACTAGTCCA GCTGTGGAAT GTGTGTCAGT TAGGG - # - #45 - - - - (2) INFORMATION FOR SEQ ID NO:10: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 48 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: SV40 geno - #me-early enhancer and promoter - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: - - CGCAGAGATC TGCATAAATA AAAAAAATTA GTCAGCCATG GGGCGGAG - # 48 - - - - (2) INFORMATION FOR SEQ ID NO:11: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 49 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: NO - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-34 TF10 provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: - - CGAGGATCCA GATCTTTGTG AAACTTCGAG GAGTCTCTTT GTTGAGGAC - # 49 - - - - (2) INFORMATION FOR SEQ ID NO:12: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 38 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: - - CAGTCGCTGC AGCGGGCGCC AACTGCGAAG TTCTCGGC - # - # 38 - - - - (2) INFORMATION FOR SEQ ID NO:13: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 32 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: - - GTCGGGCGCG CCATAATTTG CTCCACTGTA AG - # - # 32 - - - - (2) INFORMATION FOR SEQ ID NO:14: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 40 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: DNA (genomic) - - (iii) HYPOTHETICAL: NO - - (iv) ANTI-SENSE: YES - - (vi) ORIGINAL SOURCE: (A) ORGANISM: Feline Im - #munodeficiency Virus-pPPR provirus - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: - - GTCGGTCGAC GGCGCGCCTG TTCAGCTGTT TCCATTTATC - # - # 40 __________________________________________________________________________